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Regulation of HERG (KCNH2) potassium channel surface expression by diacylglycerol

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Abstract

The HERG (KCNH2) channel is a voltage-sensitive potassium channel mainly expressed in cardiac tissue, but has also been identified in other tissues like neuronal and smooth muscle tissue, and in various tumours and tumour cell lines. The function of HERG has been extensively studied, but it is still not clear what mechanisms regulate the surface expression of the channel. In the present report, using human embryonic kidney cells stably expressing HERG, we show that diacylglycerol potently inhibits the HERG current. This is mediated by a protein kinase C-evoked endocytosis of the channel protein, and is dependent on the dynein–dynamin complex. The HERG protein was found to be located only in early endosomes and not lysosomes. Thus, diacylglycerol is an important lipid participating in the regulation of HERG surface expression and function.

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Acknowledgments

This study was supported by Minerva Foundation, the Receptor Research Programme (Åbo Akademi University and University of Turku), the Sigrid Juselius Foundation, the Liv och Hälsa Foundation, the Center of Excellence in Cell Stress (Åbo Akademi University), and the Academy of Finland. K.T. was a senior investigator of the Academy of Finland during part of the study.

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Authors and Affiliations

  1. Department of Biology, Åbo Akademi University, 20520, Turku, Finland

    Cia Ramström, Emad Afrasiabi & Kid Törnquist

  2. Minerva Foundation Institute for Medical Research, Biomedicum Helsinki, 00290, Helsinki, Finland

    Cia Ramström, Hugh Chapman, Tero Viitanen, Heli Fox, Laura Korhonen, Dan Lindholm, Michael Pasternack & Kid Törnquist

  3. Department of Pharmacology and Clinical Pharmacology, University of Turku, 20520, Turku, Finland

    Johanna Kivelä & Sanna Soini

  4. Department of Biology, Åbo Akademi University, BioCity, Tykistökatu 6, 20520, Turku, Finland

    Kid Törnquist

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  1. Cia Ramström
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Ramström, C., Chapman, H., Viitanen, T. et al. Regulation of HERG (KCNH2) potassium channel surface expression by diacylglycerol. Cell. Mol. Life Sci. 67, 157–169 (2010). https://doi.org/10.1007/s00018-009-0176-2

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